Copper chelation reduces early collagen deposition and preserves saliva secretion in irradiated salivary glands.

Radiation therapy is a first-line treatment for head and neck cancer; however, it typically leads to hyposalivation stemming from fibrosis of the salivary gland. Current strategies to restore glandular function are dependent on the presence of residual functional salivary gland tissue, a condition commonly not met in patients with extensive fibrotic coverage of the salivary gland resulting from radiation therapy. Fibrosis is defined by the pathological accumulation of connective tissue (i.e., extracellular matrix) and excessive deposition of crosslinked (fibrillar) collagen that can impact a range of tissues and given that collagen crosslinking is necessary for fibrosis formation, inhibiting this process is a reasonable focus for developing anti-fibrotic therapies. Collagen crosslinking is catalyzed by the lysyl oxidase family of secreted copper-dependent metalloenzymes, and since that copper is an essential cofactor in all lysyl oxidase family members, we tested whether localized delivery of a copper chelator into the submandibular gland of irradiated mice could suppress collagen deposition and preserve the structure and function of this organ. Our results demonstrate that transdermal injection of tetrathiomolybdate into salivary glands significantly reduced the early deposition of fibrillar collagen in irradiated mice and preserved the integrity and function of submandibular gland epithelial tissue. Together, these studies identify copper metabolism as a novel therapeutic target to control radiation induced damage to the salivary gland and the current findings further indicate the therapeutic potential of repurposing clinically approved copper chelators as neoadjuvant treatments for radiation therapy.

Fibrin hydrogels fortified with FGF-7/10 and laminin-1 peptides promote regeneration of irradiated salivary glands.

Ionizing radiation, commonly used for head and neck cancer treatment, typically damages the salivary glands, resulting in hyposalivation. The development of treatments to restore this lost function is crucial for improving the quality of life for patients suffering from this condition. To address this clinical need, we have developed an innovative hydrogel by chemically conjugating laminin-1 peptides (A99 and YIGSR) and growth factors, FGF-7 and FGF-10, to fibrin hydrogels. Our results demonstrate that FGF-7/10 and laminin-1 peptides fortified fibrin hydrogel [enhanced laminin-1 peptides fibrin hydrogel (Ep-FH)] promotes salivary gland regeneration and functionality by improving epithelial tissue organization, establishing a healthy network of blood vessels and nerves, while reducing fibrosis in a head and neck irradiated mouse model. These results indicate that fibrin hydrogel-based implantable scaffolds containing pro-regenerative signals promote sustained secretory function of irradiated salivary glands, offering a potential alternative treatment for hyposalivation in head and neck cancer patients undergoing radiation treatment. These unique findings emphasize the potential of fibrin hydrogel-based implantable scaffolds enriched with pro-regenerative signals in sustaining the secretory function of irradiated salivary glands and offer a promising alternative treatment for addressing hyposalivation in head and neck cancer patients undergoing radiation therapy. STATEMENT OF SIGNIFICANCE: Radiation therapies used to treat head and neck cancers often result in damaged salivary gland, leading to severe dryness of the oral cavity. In this study, we engineered FGF-7 and FGF-10 and immobilized them into L1p-FH. The resulting hydrogel, Ep-FH, restored irradiated salivary gland functionality by enhancing epithelial tissue organization, promoting the development of a healthy network of blood vessels and nerves as well as reduction of fibrosis.

Cemented vs Uncemented hemiarthroplasties for femoral neck fractures: An overlapping systematic review and evidence appraisal.

BACKGROUND: The purpose of our study is to assess the methodology of overlapping systematic reviews related to cemented vs uncemented hip hemiarthroplasties for the treatment of femoral neck fractures to find the study with the best evidence. Also, we assess the gaps in methodology and information to help with direction of future studies. METHODS: A systematic search was conducted in September 2022 using Pubmed, Embase, and Cochrane Library. Clinical outcome data and characteristics of each study were extracted to see which treatment had better favorability. The outcomes and characteristics extracted from each study includes, first author, search date, publication journal and date, number of studies included, databases, level of evidence, software used, subgroup analyses that were conducted, and heterogeneity with the use of I2 statistics Methodological quality information was extracted from each study using four different methodologic scores (Oxford Levels of Evidence; Assessment of Multiple Systematic Reviews (AMSTAR); Quality of reporting of meta-analyses (QUROM); Oxman and Guyatt. After that, the Jadad decision algorithm was used to identify which studies in our sample contained the best available evidence. Finally, overlap of each systematic review was assessed using Corrected Covered Area (CCA) to look at redundancy and research waste among the systematic reviews published on the topic. RESULTS: After screening, 12 studies were included in our sample. For the Oxford Levels of Evidence, we found that all the studies were Level I evidence. For the QUORUM assessment, we had 1 study with the highest score of 18. Additionally, we did the Oxman and Guyatt assessment, where we found 4 studies with a maximum score of 6. Finally, we did an AMSTAR assessment and found 2 studies with a score of 9. After conducting the methodological scores; the authors determined that Li. L et al 2021 had the highest quality. In addition, it was found that the CCA found among the primary studies in each systematic review calculated to .22. Any CCA above .15 is considered "very high overlap". CONCLUSIONS: The best available evidence suggests that Cemented HAs are better at preventing Prosthesis-related complications. Conversely, the best evidence also suggests that Cemented HA also results in longer operative time and increased intraoperative blood loss. When conducting future systematic reviews related to the topic, we ask that authors restrict conducting another systematic review until new evidence emerges so as not to confuse the clinical decision-making of physicians.

Tuft Cells Are Present in Submandibular Glands Across Species.

Tuft cells are bottle-shaped, microvilli-projecting chemosensory cells located in the lining of a variety of epithelial tissues and, following their identification approximately 60 years ago, have been linked to immune system function in a variety of epithelia. Until recently, Tuft cells had not been convincingly demonstrated to be present in salivary glands with their detection by transmission electron microscopy only shown in a handful of earlier studies using rat salivary glands, and no follow-up work has been conducted to verify their presence in salivary glands of other species. Here, we demonstrate that Tuft cells are present in the submandibular glands of various species (i.e., mouse, pig and human) using transmission electron microscopy and confocal immunofluorescent analysis for the POU class 2 homeobox 3 (POU2F3), which is considered to be a master regulator of Tuft cell identity.

Inadequate Reporting of Complications in Randomized Controlled Trials Cited as Supporting Evidence Underpinning AAOS CPG Recommendations for Hip and Knee Osteoarthritis: Application of the CONSORT Harms Checklist.

BACKGROUND: Randomized controlled trials (RCTs) have been shown to influence clinical decision-making and health policy. Therefore, it is essential that trial outcomes-including harms-are completely reported. METHODS: We included all RCTs cited as supporting evidence for the American Academy of Orthopaedic Surgeons Surgical Management of Osteoarthritis of the Knee, Osteoarthritis of the Knee, and Osteoarthritis of theHip Clinical Practice Guideline recommendations. Manuscripts were analyzed for compliance with the Consolidated Standards of Reporting Trials (CONSORT) Extension for Harms items. We determined the Extension for Harms' influence on harms reporting by comparing RCTs published before and after the extension's release. RESULTS: One hundred and seventy-three RCTs were included, of which 81 (47%) adequately reported ≥50% of the checklist and 75 (43%) reported ≤33% of the checklist items. The mean number of checklist items reported was 8 items (of 18; 45%). Our interrupted time-series analysis suggests the implementation of the CONSORT Extension for Harms did not have a statistically significant effect on the completeness of harms reporting (P = .35; 95% Confidence interval = -0.0041 to 0.0014). CONCLUSION: Harms-related data are poorly reported within RCTs cited as supporting evidence for the American Academy of Orthopaedic Surgeons management for hip and knee OA Clinical Practice Guideline. Our time series analysis illustrates the failure of the CONSORT Extension for Harms on improving the reporting of harms-related data. Future efforts to improve the quality of harms reporting is crucial for patients, clinicians, and policy makers to perform thorough risk-benefit appraisals as RCT results directly influence clinical decision-making in orthopaedic surgery.

Evaluation of spin in the abstracts of systematic reviews and meta-analyses covering surgical management, or quality of life after surgical management, of osteoarthritis of the knee.

Objective: Our primary objective was to identify the prevalence of spin - misleading reporting practices that overemphasize benefit or underemphasize harm - within the abstracts of systematic reviews and meta-analyses focused on surgical management of osteoarthritis of the knee. Methods: A search string was developed to search Ovid MEDLINE and Ovid Embase for articles pertaining to surgical management, or quality of life after surgical management, of osteoarthritis of the knee. Titles and abstracts were screened according to our protocol, developed a priori, followed by full-text evaluation for spin in included articles. Study characteristics were simultaneously extracted with spin data and each included study received an AMSTAR-2 quality appraisal. All procedures were performed by two examiners in a masked, duplicate fashion. Results: Of the 1419 articles returned, 96 systematic reviews qualified for inclusion. 35.4% of the included abstracts (34/96) contained at least one type of spin with a total of 36 occurrences (two abstracts contained two types of spin). Selective reporting favoring benefit (type 3; 15/36, 41.7%) was the most prevalent followed by selective reporting of harms (type 6; 7/36, 19.4%). None of the abstracts contained spin types 2, 4, or 8. We found no significant association between spin and either AMSTAR-2 rating or extracted study characteristics. Conclusion: Of the included systematic reviews and meta-analyses, 35.4% contained spin in their abstract. To improve the reliability of systematic reviews and meta-analyses, researchers should act to minimize spin in future abstracts.

Allogenic blood transfusion following total hip arthroplasty: results from the nationwide inpatient sample, 2000 to 2009.

BACKGROUND: The large-scale utilization of allogenic blood transfusion and its associated outcomes have been described in critically ill patients and those undergoing high-risk cardiac surgery but not in patients undergoing elective total hip arthroplasty. The objective of this study was to determine the trends in utilization and outcomes of allogenic blood transfusion in patients undergoing primary total hip arthroplasty in the United States from 2000 to 2009. METHODS: An observational cohort of 2,087,423 patients who underwent primary total hip arthroplasty from 2000 to 2009 was identified in the Nationwide Inpatient Sample. International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes 99.03 and 99.04 were used to identify patients who received allogenic blood products during their hospital stay. Risk factors for allogenic transfusions were identified with use of multivariable logistic regression models. We used propensity score matching to estimate the adjusted association between transfusion and surgical outcomes. RESULTS: The rate of allogenic blood transfusion increased from 11.8% in 2000 to 19.0% in 2009. Patient-related risk factors for receiving an allogenic blood transfusion include an older age, female sex, black race, and Medicaid insurance. Hospital-related risk factors include rural location, smaller size, and non-academic status. After adjusting for confounders, allogenic blood transfusion was associated with a longer hospital stay (0.58 ± 0.02 day; p < 0.001), increased costs ($1731 ± $49 [in 2009 U.S. dollars]; p < 0.001), increased rate of discharge to an inpatient facility (odds ratio, 1.28; 95% confidence interval, 1.26 to 1.31), and worse surgical and medical outcomes. In-hospital mortality was not affected by allogenic blood transfusion (odds ratio, 0.97; 95% confidence interval, 0.77 to 1.21). CONCLUSIONS: The increase in allogenic blood transfusion among total hip arthroplasty patients is concerning considering the associated increase in surgical complications and adverse events. The risk factors for transfusion and its impact on costs and inpatient outcomes can potentially be used to enhance patient care through optimizing preoperative discussions and effective utilization of blood-conservation methods.

Primary total knee arthroplasty allogenic transfusion trends, length of stay, and complications: nationwide inpatient sample 2000-2009.

Perioperative blood loss leading to blood transfusion continues to be an issue for total knee arthroplasty (TKA) patients. The US Nationwide Inpatient Sample (NIS) was used to determine annual trends in allogenic blood transfusion rates, and effects of transfusion on in-hospital mortality, length of stay (LOS), costs, discharge disposition, and complications of primary TKA patients. TKA patients between 2000 and 2009 were included (n = 4,544,999) and categorized as: (1) those who received a transfusion of allogenic blood, and (2) those who did not. Transfusion rates increased from 7.7% to 12.2%. For both transfused and not transfused groups, mortality rates and mean LOS declined, while total costs increased. Transfused patients were associated with adjusted odds ratios of in-hospital mortality (AOR 1.16; P = 0.184), 0.71 ± 0.01 days longer LOS (P < 0.0001), and incurred ($1777 ± 36; P < 0.0001) higher total costs per admission.

Comparison of acetabular shell position using patient specific instruments vs. standard surgical instruments: a randomized clinical trial.

Total hip arthroplasty (THA) survivorship relies largely upon appropriate acetabular cup placement. The purpose of this prospective randomized controlled trial was to determine whether the use of a preoperative 3D planning software in combination with patient specific instrumentation (PSI) results in improved cup placement compared with traditional techniques. Thirty-six THA patients were randomized into standard (STD) or PSI technique. Standard approach was completed using traditional techniques, while PSI cases were planned and customized surgical instruments were manufactured. Postoperative CT scans were used to compare planned to actual results. Differences found between planned and actual anteversion were -0.2° ± 6.9° (PSI) and -6.9°±8.9° (STD) (P = 0.018). Use of 3D preoperative planning along with PSIs resulted in significantly greater anteversion accuracy than traditional planning and instrumentation.

Dedicated orthopedic operating room unit improves operating room efficiency.

We investigated the effectiveness of dedicated orthopedic operating rooms (OR) on minimizing time spent on perioperative processes to increase OR throughput in total knee and hip arthroplasty procedures. The use of a dedicated orthopedic unit that included 6 ORs with staff allocated only for those ORs was compared to the use of a traditional staffing model. After matching to simulate randomization, each group consisted of 422 procedures. The dedicated orthopedic unit improved average anesthesia controlled time by 4 minutes (P<.001), operative time by 7 minutes (P=.004) and turnover time by 8 minutes (P<.001). An overall improvement of 19 minutes per procedure using the dedicated unit was observed. Utilizing a dedicated orthopedic unit can save time without increasing adverse events.